Life's Essential 8 and osteoporosis in adults aged 50 years or older: data from the National Health and Nutrition Examination Survey.

In this cross-sectional study, we examined the association between Life's Essential 8 (LE8) and bone mineral density (BMD) as well as osteoporosis risk among adults aged 50 and over. The findings of this study revealed that higher LE8 scores were associated with higher BMD and reduced osteoporosis risk. PURPOSE: The objective of the present study was to evaluate the association between Life's Essential 8 (LE8) and bone mineral density (BMD), as well as osteoporosis risk, in adults aged 50 years or over. METHODS: This cross-sectional study recruited individuals who were 50 years old or older from the National Health and Nutrition Examination Survey. LE8 scores were evaluated and calculated according to the scoring algorithm based on the American Heart Association recommendations, which were further categorized into health behaviors (LE8-HB) and health factors (LE8-HF) scores. Furthermore, the present study utilized multivariate linear regression models to examine the correlations between BMD and LE8 scores. In addition, ordinal logistic regression models were employed to determine the associations between the risk of osteoporosis (normal BMD, osteopenia, and osteoporosis) and LE8 scores. RESULTS: The final analysis included a total of 2910 participants, whose mean age was 64.49 ± 9.28 years. LE8 and LE8-HF scores exhibited a negative association with BMD and a positive association with osteoporosis risk in unadjusted models. Nevertheless, after adjustment for covariates, LE8 and LE8-HB scores exhibited a positive association with BMD and a negative association with osteoporosis risk, regardless of age, sex, or menopausal status. CONCLUSIONS: Scoring systems based on multiple lifestyle and behavior factors, similar to LE8, have the potential to become a novel option and be used for osteoporosis risk assessment.

The effect of perioperative sequential application of multiple doses of tranexamic acid on postoperative blood loss after PLIF: a prospective randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) has been utilized in spinal surgery to effectively reduce intraoperative blood loss (IBL) and allogeneic blood transfusion rates. However, the traditional TXA regimen might last the entire duration of hyperfibrinolysis caused by surgical trauma, resulting in its limited ability to reduce postoperative blood loss (PBL). Therefore, the aim of this study was to investigate the effectiveness of perioperative sequential administration of multiple doses of TXA in reducing PBL in patients who underwent posterior lumbar interbody fusion (PLIF). METHODS: From October 2022 to June 2023, 231 patients who were diagnosed with lumbar degenerative disease and scheduled to undergo PLIF were prospectively enrolled in the present study. The patients were randomly divided into three groups. Moreover, all patients received an intravenous injection of TXA at a dose of 15 mg/kg 15 min before the surgical skin incision. Patients in Group A received a placebo of normal saline after surgery, while patients in Group B received three additional intravenous injections of TXA at a dose of 15 mg/kg every 24 h. Patients in Group C received three additional intravenous injections of TXA at a dose of 15 mg/kg every 5 h. The primary outcome measure was PBL. In addition, this study assessed total blood loss (TBL), IBL, routine blood parameters, liver and kidney function, coagulation parameters, fibrinolysis indexes, inflammatory indicators, drainage tube removal time (DRT), length of hospital stay (LOS), blood transfusion rate, and incidence of complications for all subjects. RESULTS: The PBL, TBL, DRT, and LOS of Group B and Group C were significantly lower than those of Group A ( P <0.05). The level of D-dimer (D-D) in Group C was significantly lower than that in Group A on the first day after the operation ( P =0.002), and that in Group B was significantly lower than that in Group A on the third day after the operation ( P =0.003). The interleukin-6 levels between the three groups from 1 to 5 days after the operation were in the order of Group A > Group B > Group C. No serious complications were observed in any patient. The results of multiple stepwise linear regression analysis revealed that PBL was positively correlated with incision length, IBL, smoking history, history of hypertension, preoperative fibrinogen degradation product level, and blood transfusion. It was negatively correlated with preoperative levels of fibrinogen, red blood cells, blood urea nitrogen, and age. Compared to female patients, male patients had an increased risk of PBL. Finally, the incidence of PBL was predicted. CONCLUSIONS: Sequential application of multiple doses of TXA during the perioperative period could safely and effectively reduce PBL and TBL, shorten DRT and LOS, reduce postoperative D-D generation, and reduce the postoperative inflammatory response. In addition, this study provided a novel prediction model for PBL in patients undergoing PLIF.

Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery.

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment.

The effect of sequential perioperative intravenous tranexamic acid in reducing postoperative blood loss and hidden blood loss after posterior lumbar interbody fusion: a randomized controlled trial.

Background: Tranexamic acid (TXA) has previously been shown to be effective in reducing intraoperative blood loss (IBL) and transfusion requirements in spine surgery. A conventional TXA regimen is a simple preoperative or intraoperative administration. However, the hyperfibrinolysis caused by surgical trauma lasts at least 24 h, and a single dose of TXA cannot cover the whole process of hyperfibrinolysis. Moreover, its ability to control postoperative blood loss (PBL) may be insufficient. Therefore, this study aimed to explore the effects and safety of sequential perioperative intravenous TXA for reducing bleeding after posterior lumbar interbody fusion (PLIF). Methods: Patients requiring PLIF were randomly divided into two groups. All patients were intravenously injected with 1 g of TXA 15 min before skin resection. Every day after the surgery, 200 ml saline was intravenously injected for 1-3 days in Group A, while Group B received 1 g of TXA instead of saline. The total blood loss (TBL), IBL, PBL, HCT, Hb, blood transfusion volume, inflammation-related indicators, and complications were recorded. Results: TBL, PBL, and hidden blood loss (HBL) in Group B were significantly lower than those in Group A (P < 0.05). The maximum decreases in HCT and Hb in Group B were also significantly lower than those in Group A (P < 0.05), and the drainage removal time (DRT) was sooner in Group B than in Group A (P = 0.003). On the 3rd and 5th days after surgery, the level of CRP in Group B was significantly lower than that in Group A (P < 0.05). Similarly, IL-6 levels were significantly lower in Group B for the first 5 days postoperatively (P < 0.001). Sex, operation time, level of decompression, length of incision, and change in HCT were significant predictors of both TBL and HBL. TBL was also significantly associated with BMI and preoperative fibrinogen, while postoperative TXA was a significant predictor of HBL only. Conclusion: Intravenous injection of 1 g of TXA 15 min before skin resection combined with continuous intravenous injection of 1 g of TXA 1 to 3 days after PLIF can reduce postoperative bleeding and shorten the time to drainage tube removal. In addition, it can also inhibit the postoperative inflammatory response. Clinical trial registration: ChiCTR2200056210.

Clinical application of a modified predeposit autologous red blood cell apheresis in multistage spinal fusion: a single-center retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of predeposit autologous RBC apheresis (PARA) in patients undergoing multilevel spinal fusion surgery. Methods: A total of 112 patients from January 2020 to June 2022 were divided into two groups according to PARA: the PARA group (n = 51) and the control group (n = 61). The baseline characteristics of the patients, outcomes, transfusion cost, hospitalization cost, length of stay, complications, and changes in hemoglobin and hematocrit levels between the two groups were compared. Results: The baseline characteristics were similar in both groups. No significant differences were found in functional outcomes, including VAS score (p = 0.159), ODI score (p = 0.214), JOA score (p = 0.752), and SF-36 score (p = 0.188) between the PARA and control groups. The amount and rate of intraoperative and perioperative allogeneic RBC transfusion were significantly higher in the control group than in the PARA group (p < 0.001). The postoperative (9.04 ± 3.21 vs. 11.05 ± 3.84, p = 0.004) and total length of stay (15.78 ± 3.79 vs. 17.36 ± 4.08, p = 0.038) in the PARA group were significantly lower than those in the control group, respectively. Despite no difference in hospitalization cost (p = 0.737), the total blood transfusion cost in the PARA group was significantly lower, compared with the control group (p < 0.001). For safety evaluation, there were no significant differences in Hb and Hct levels between the two groups at admission, on postoperative day 1, and postoperative day 3, respectively (p > 0.05). Moreover, the number of postoperative infections in the PARA group was significantly lower than that in the control group (p = 0.038). Conclusion: PARA was a novel, safe, and highly efficient technique for mass autologous blood preparation in a quite short preparation time. This method could significantly reduce the amount of allogeneic blood transfusion and length of stay, which could provide a theoretical basis for following clinical practice about the technique.

Efficacy and Safety of Erector Spinae Plane Block for Perioperative Pain Management in Lumbar Spinal Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Since the application of ultrasound-guided erector spinae plane block (ESPB) in 2016, the approach has been gradually applied to perioperative analgesia in various surgeries. In recent years, more and more studies have focused on the effect of ESPB in perioperative analgesia of lumbar spinal surgery, but its clinical effect remains controversial. Objective: This systematic review and meta-analysis was designed to explore the efficacy and safety of ESPB used for perioperative pain management in lumbar spinal surgery. Methods: The Pubmed, Web of Science, Cochrane Library, and EMBASE databases were comprehensively searched for relevant articles from inception to March 2022. Randomized controlled trials (RCTs) comparing ESPB with placebo or without ESPB in lumbar spinal surgery were included. The Review Manager 5.3 software was employed for this meta-analysis. Results: Nineteen RCTs with 1381 participants were included for final analysis. ESPB group exhibited lower intraoperative consumption of sufentanil and remifentanil, lower total opioid consumption within 24 h and 48 h after surgery, lower incidence of rescue analgesia, longer time to first rescue analgesic and lower number of PCA button presses compared to the control group (P<0.05). Moreover, the ESPB group had significantly lower pain scores at rest and on movement within 48 h after surgery compared with the control group (P<0.05). In terms of opioid-related adverse reactions, ESPB reduced the incidence of postoperative nausea, vomitting, somnolence and itching in comparison to the control group (P<0.05). ESPB-related serious complications were not reported in included studies. Conclusion: This meta-analysis demonstrated that ESPB used in lumbar spinal surgery was effective in relieving postoperative pain, decreasing the perioperative consumption of opioids, as well as decreasing the incidence of postoperative opioid-related adverse reactions.

Ultrasonic-controlled "explosive" hydrogels to precisely regulate spatiotemporal osteoimmune disturbance.

Spatiotemporal Immune disorder is a key factor leading to the failure of bone tissue healing. It is of vital importance to accurately suppress excessive peak immune response within 24-48 h of the injury and so regulate the spatiotemporal osteoimmune disturbance of bones. In this study, Ultrasound Controlled "Explosive" (UCE) hydrogels were prepared from gelatin-hyaluronic acid methacrylate hydrogels loaded with resveratrol nanobubbles produced by double emulsification through a condensation reaction. Such materials innovatively enable ultrasound-controlled RES release for precise regulation of spatiotemporal osteoimmune disorders. Under an ultrasonic power level of 1.5 W/cm2, the rate of effectively released RES through the blast of UCE hydrogels reached 38.14 %. And compared with the control group, the in vivo inhibition of inflammation and osteogenesis effects of UCE hydrogels were more effective, respectively. As suggested by the results, the excessive local inflammatory response was inhibited by the release of resveratrol, the temporospatial disorder of bone immune was precisely regulated, and as a result, the process of bone repair was accelerated. Altogether, this study confirms that the newly created UCE Hydrogels effectively promote bone repair by intervening peak inflammation during the early phase of fracture healing.

A systematic review and meta-analysis of cemented and uncemented bipolar hemiarthroplasty for the treatment of femoral neck fractures in elderly patients over 60 years old.

Background: Currently, whether bone cement can be applied in bipolar hemiarthroplasty to treat femoral neck fractures (FNFs) in elderly patients is controversial. The aim of this systematic review and meta-analysis was to compare the effectiveness and safety of cemented bipolar hemiarthroplasty (CBH) versus uncemented bipolar hemiarthroplasty (UCBH) in the treatment of FNFs among elderly patients over 60 years old. Materials and methods: The Pubmed, Web of science, Cochrane Library and EMBASE databases were searched comprehensively for relevant articles from their inception to May 2022. Studies about comparing outcomes between CBH and UCBH for FNFs in elderly patients aged more than 60 years were included. Outcomes including operation time, intra-operative blood loss, length of hospital stay, wound infections, residual pain, revisions, re-operations, complications related to prosthesis, general complications, and mortality. The Review Manager 5.3 software provided by the Cochrane Collaboration Network was used to perform the meta-analysis of comparable data. Results: A total of 6 randomized controlled trials (RCTs) and 9 observational studies were included in this analysis, with 33,118 patients (33,127 hips). Results of the meta-analysis indicated that the operation time [WMD = 13.01 min, 95% CI (10.79, 15.23)], intra-operative blood loss [WMD = 80.57 ml, 95% CI (61.14, 99.99)], incidence of heterotrophic ossification [OR = 2.07, 95% CI (1,14, 3.78)], were increased in the CBH group but the incidence of intra-operative fractures [OR = 0.24, 95% CI (0.07, 0.86)], periprosthetic fractures [OR = 0.24, 95% CI (0.18, 0.31)], aseptic loosening of prosthesis [OR = 0.20, 95% CI (0.09, 0.44)], wound infections [OR = 0.80, 95% CI (0.68, 0.95)] and re-operation rates [OR = 0.61, 95% CI (0.54, 0.68)] were lower in the CBH group by comparison with the UCHB group. However, there were no significant differences in residual pain, length of hospital stay, prosthetic dislocation, prosthetic subsidence (> 5 mm), acetabulum erosion, revisions, pulmonary infections, pulmonary embolisms, urinary tract infections, deep venous thromboses, decubitus, cardiovascular accidents (arrhythmia/myocardial infarction), and respiratory failure between the two groups. In terms of mortality, perioperative mortality (within 72 h) [OR = 2.39, 95% CI (1.71, 3.32)] and 1-week mortality postoperatively [OR = 1.22, 95% CI (1.05, 1.41)] in CBH group were higher than those in UCBH group, but there were no significant differences in mortality at 1 month, 3 months, 1 year, and 2 years postoperatively between CBH group and UCBH group. Conclusion: This meta-analysis found that elderly patients over 60 years old with FNFs who underwent CBH had longer operation time, higher incidence of heterotrophic ossification, intra-operative blood loss, and mortality within 72 h of operation and at 1-week postoperatively, but lower incidence of periprosthetic fractures, aseptic loosening of prosthesis, intra-operative fractures, wound infections and re-operations. Other outcomes were not significantly different between the two groups. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021274253.

Changes in Bone Turnover Markers after Osteoporotic Vertebral Compression Fractures in Males and Females.

Background: To explore the normal changes in bone turnover markers (BTMs) and the correlations between the different BTMs after osteoporotic vertebral compression fracture (OVCF). Meanwhile, we explored the related differences that exist between sexes. Methods: A total of 130 OVCF patients were retrospectively reviewed. Using IBM SPSS 19.0 statistical software, the differences in the levels of BTMs and clinical parameters between sexes were assessed using Student's unpaired t test, and one-way ANOVA was used for the comparison of the three groups of samples. The correlations between P1NP, CTX, and clinical factors were assessed using Pearson's correlation coefficient. Results: P1NP was 52.15 ng/ml within two weeks in male patients, and the level increased to 96.33 ng/ml after 12 weeks; in female patients, the increase was not as obvious as in male patients. CTX in male patients reached as much as approximately twice the initial value after 12 weeks. However, the situation in female patients was diverse. CTX was 0.58 ng/ml within two weeks and increased to 0.61 ng/ml within 2-12 weeks after the onset of OVCF. Subsequently, CTX decreased suddenly after 12 weeks. The increase in P1NP levels within 2 weeks after OVCF was significantly correlated with the levels of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Changes in CTX within 2 weeks after OVCF were considerably related to phosphorus, 25 hydroxyvitamin D (25-OHD), OC, and BAP. Conclusion: The levels of P1NP and CTX increased differently in males and females after OVCF. The levels of OC and BAP were correlated with the levels of P1NP and CTX within 2 weeks of OVCF.

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis.

Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication. However, these boundary layers can be damaged by shear, resulting in decreased lubrication. Here, a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib (CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid (HA) hydrogels (CLX@Lipo@HA-gel). The dynamic cross-linked network enables the hydrogel to get restructured in response to shear, and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces, which results in the formation of boundary layers to provide stable lubrication. Moreover, hydration shells formed surrounding the hydrogel can retard the degradation process, thus helping in sustaining lubrication. Furthermore, in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance, alleviate cartilage wear, and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication. Overall, CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis.

SIRT1 alleviates IL-1ß induced nucleus pulposus cells pyroptosis via mitophagy in intervertebral disc degeneration.

Inflammatory stress of nucleus pulposus cells (NPCs) plays an important role in the pathogenesis of intervertebral disc degeneration (IVDD). Pyroptosis and NLRP3 inflammasome activation have been reported aggravating IVDD. SIRT1 is essential for mammalian cell survival and longevity by participating in various cellular processes. However, few studies analyzed the potential mechanism of SIRT1 in NLRP3- activated pyroptosis in NPCs. In this study, we confirmed that IL-1ß could induce pyroptosis and NLRP3 inflammation activation, meanwhile, resulted in mitochondrial oxidative stress injury and dysfunction in NPCs. When the mitochondrial ROS was inhibited by Mito-Tempo, the pyroptosis and NLRP3 inflammation activation was also inhibited. SIRT1 overexpression could ameliorate IL-1ß induced mitochondrial dysfunction and ROS accumulation, inhibit NLRP3 inflammasome activation by promoting PINK1/Parkin mediated mitophagy, however, these protective phenomena reversed by autophagy inhibitor 3-MA pretreatment. In vivo, SIRT1 agonist (SRT1720) treatment decreased the expression of NLRP3, p20, and IL-1ß, increased the expression of PINK1 and LC3, delayed IVDD process in the rat model. Taken together, our results indicate that SIRT1 alleviates IL-1ß induced NLRP3 inflammasome activation via mitophagy in NPCs, SIRT1 may be a potential therapeutic target to alleviate NLRP3- activated pyroptosis in the inflammatory stress related IVDD.

Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration.

Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition. Herein, an injectable microsphere (MS@MCL) for local lactate exhaustion was constructed by grafting manganese dioxide (MnO2) -lactate oxidase (LOX) composite nanozyme on microfluidic hyaluronic acid methacrylate (HAMA) microspheres via chemical bonds, achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo. The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency. Furthermore, chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement. It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells (NPCs) in vitro. In the rat degenerative intervertebral disc model caused by lactate injection, MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix (ECM) degradation as well as inflammatory damage in vivo. Altogether, this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.

Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis.

Introducing hydration layers to hydrogel microspheres (HMs) by coating the surface with liposomes can effectively reduce friction. However, the lubrication can be inactivated when the surface coatings are damaged. To endow HMs with the ability to form self-renewable hydration layers and maintain cellular homeostasis, rapamycin-liposome-incorporating hyaluronic acid-based HMs (RAPA@Lipo@HMs) were created using microfluidic technology and photopolymerization processes. The RAPA@Lipo@HMs improve joint lubrication by using a smooth rolling mechanism and continuously exposing liposomes on the outer surface to form self-renewable hydration layers via frictional wear. In addition, the released autophagy activator (rapamycin)-loaded cationic liposomes can target negatively charged cartilage through electrostatic interactions and maintain cellular homeostasis by increasing autophagy. Furthermore, the in vivo data showed that the RAPA@Lipo@HMs can alleviate joint wear and delay the progression of osteoarthritis. The RAPA@Lipo@HMs can provide efficient lubrication and potentially alleviate friction-related diseases such as osteoarthritis.

Use of a Multifunctional Cocktail for Postoperative Bleeding and Pain Control in Spinal Fusion: A Randomized, Double-blind, Controlled Trial.

STUDY DESIGN: A prospective, randomized, double-blind controlled trial. OBJECTIVE: To explore the effect of multifunctional cocktail for bleeding and pain control after spinal fusion. SUMMARY OF BACKGROUND DATA: Managing postoperative bleeding and pain after spinal fusion remains a challenge. Topical application of tranexamic acid or anesthetic agents for bleeding or pain management just started recently, and the multifunctional cocktail for bleeding and pain control simultaneously after spinal fusion have never been published. METHODS: Ninety patients who underwent posterior spinal fusion were enrolled in this study. The multifunctional cocktail was injected into the incision before wound closure in the cocktail group. In the control group, an equal volume of normal saline was injected and a patient-controlled analgesic pump was used. Visual analogue scale score; opioid consumption; intraoperative, postoperative, hidden and total blood loss; volume of drainage, hematocrit levels of drainage; hemoglobin levels; and complications were compared between the two groups. RESULTS: There were no differences in the visual analogue scale within 48 hours after surgery between the two groups. However, the opioid dosages in the control group were higher than those in the cocktail group. The postoperative blood loss, total blood loss, and hidden blood loss were lower in the cocktail group than in the control group. The drainage volume showed no differences between the two groups; however, the hematocrit level of drainage at 24 hours after surgery was lower in the cocktail group than in the control group. The hemoglobin level was higher in the cocktail group than in the control group at postoperative day 3. Thirteen patients with unbearable nausea and vomiting in the control group, whereas no complications in the cocktail group. CONCLUSION: Topical application of a multifunctional cocktail that we designed provides an effective and safe method for reducing pain and bleeding after spinal fusion.

LIPUS inhibits inflammation and catabolism through the NF-κB pathway in human degenerative nucleus pulposus cells.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is a safe and noninvasive rehabilitative physical therapy with anti-inflammatory effects. The current study investigated the effect of LIPUS on the inflammation of nucleus pulposus (NP) cells and its underlying mechanism. METHODS: Human NP cells were acquired from lumbar disc herniation tissue samples and cultured for experiments. Human NP cells were treated with LPS and then exposed to LIPUS (15 mW/cm2, 30 mW/cm2 and 60 mW/cm2) for 20 min daily for 3 days to determine the appropriate intensity to inhibit the expression of the inflammatory factors TNF-α and IL-1ß. The gene and protein expression of aggrecan, collagen II, MMP-3 and MMP-9 was measured by real-time PCR and western blotting, respectively. The activity of the nuclear factor-kappa B (NF-κB) pathway was examined by western blotting and immunofluorescence. After pretreatment with the NF-κB inhibitor PDTC, the expression of TNF-α, IL-1ß, MMP-3 and MMP-9 was measured by real-time PCR. RESULTS: LIPUS at intensities of 15 mW/cm2, 30 mW/cm2 and 60 mW/cm2 inhibited LPS-induced NP cell expression of the inflammatory factors TNF-α and IL-1ß, especially at 30 mW/cm2. LIPUS significantly upregulated the gene and protein expression of aggrecan and collagen II and downregulated the gene and protein expression of MMP-3 and MMP-9 in LPS-induced NP cells. The NF-κB signaling pathway was inhibited by LIPUS through inhibiting the protein expression of p-P65 and the translocation of P65 into the nucleus in LPS-induced NP cells. In addition, LIPUS had similar effects as the NF-κB inhibitor PDTC by inhibiting the NF-κB signaling pathway, inflammation and catabolism in LPS-induced human degenerative nucleus pulposus cells. CONCLUSION: LIPUS inhibited inflammation and catabolism through the NF-κB pathway in human degenerative nucleus pulposus cells.

LDHA-Mediated Glycolytic Metabolism in Nucleus Pulposus Cells Is a Potential Therapeutic Target for Intervertebral Disc Degeneration.

The intervertebral disc degeneration (IDD) is considered to be an initiator of a series of spinal diseases, among which changes in the nucleus pulposus (NP) are the most significant. NP cells reside in a microenvironment with a lack of blood vessels, hypoxia, and low glucose within the intervertebral disc. Due to the strong activity of HIF-1α, glycolysis is the main pathway for energy metabolism in NP cells. Our previous study found that higher SIRT1 expression is beneficial to delay the degeneration of NP cells. In order to find the downstream genes by which SIRT1 acts on NP cells, we used iTRAQ sequencing to detect the differences between degenerated NP cells overexpressing SIRT1 and a control group (human NP cells were derived from surgery) and found that the expression of LDHA changed in the same direction with SIRT1. This suggests that SIRT1 may delay the degeneration of NP cells by regulating glycolysis. We then used a Seahorse XFe24 analyzer to measure the bioenergetic parameters of NP cells and obtained three findings: (a) glycolysis is the main energy metabolism pathway in NP cells, (b) there is a large difference in ATP production between senescent cells and young cells, and (c) SIRT1 can regulate the production of ATP from glycolysis by regulating LDHA. We also found that SIRT1 in NP cells has a positive regulatory effect on c-Myc which is an upstream gene of LDHA. Through observing IDD-related indicators such as apoptosis, proliferation, senescence, and extracellular matrix, we found that SIRT1 can delay degeneration, and interference with c-Myc and LDHA, respectively, weakens the protective effect of SIRT1. Interfering with LDHA alone can also inhibit glycolysis and accelerate degeneration. Overall, we found that the inhibition of glycolysis in Np cells significantly affects their normal physiological functions and determined that LDHA is a potential therapeutic target for the treatment of IDD.

DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1ß mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA (DNAHA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed DNAHA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.

One-stage posterior laminectomy with instrumented fusion and foraminotomy for cervical ossification of posterior longitudinal ligament with radiculopathy pain.

OBJECTIVE: To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs METHODS: Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI. RESULTS: All the 48 patients were followed up for 24-42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2-C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group. CONCLUSIONS: One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.

The influence of topical use of tranexamic acid in reducing blood loss on early operation for thoracolumbar burst fracture: a randomized double-blinded controlled study.

PURPOSE: To investigate the safety and efficacy of topical use of tranexamic acid (TXA) on early operation for thoracolumbar burst fracture (TBF). METHODS: Patients with acute TBF requiring early decompression were prospectively collected. The enrolled patients were randomly assigned to TXA and control group, in which wound surface was soaked with TXA or the same volume of normal saline for 5 min after wound incision, respectively. The total blood loss (TBL), intraoperative blood loss (IBL), postoperative blood loss (PBL), hemoglobin (HGB) levels on preoperatively (pre-op) and postoperatively, and amount of allogenic blood transfusion were recorded. Furthermore, the general information was also compared between groups. RESULTS: There were 39 and 37 patients enrolled in TXA and control group for final analysis. The demographics data showed no significant difference between groups (P > 0.05), but operation time and IBL were significantly decreased in TXA group (P < 0.05). Further analysis showed that HGB level was significantly higher in the TXA group at POD1, while the TBL and PBL were significantly less than those in the control group (P < 0.05), but similar to HBL (P > 0.05). The postoperative ambulation time, removal time of drainage tube, length of hospital stay, and blood transfusion rate were also significantly less in TXA group (P < 0.05). At the final follow-up, no neurological deteriorations and no TXA-related complications were observed in both groups. CONCLUSION: This RCT first demonstrated that topical TXA usage after wound incision could effectively reduce IBL without increasing risk of complications, beneficial to enhanced recovery after early operation for TBF.

Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs). With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.